Value of a run-in period in a drug trial during pregnancy

The Vaginal Infections and Prematurity (VIP) Study included a clinical trial of the efficacy of erythromycin in preventing adverse pregnancy outcomes. A prerandomization run-in period was part of the trial design. During this period, women were given 1 week's supply of placebo pills to test their compliance. Those who met certain criteria for compliance, were otherwise still eligible, and agreed to participate were then randomized to receive erythromycin or placebo for a maximum of 10 weeks. During 2 years of the VIP Study, 1476 (71%) of 2071 women who began the run-in period were randomized. Women at least 30 years of age, those not smoking during pregnancy or shortly before pregnancy, and those still working outside the home at the time of enrollment were more likely than other women to be randomized after the run-in. Calculations of relative efficiency, based on a standard sample-size formula, suggest that the VIP run-in procedure not only eliminated potentially noncompliant women before randomization but also increased the power of the trial. Similar calculations which incorporated costs suggest that the run-in also resulted in lower costs, compared to a trial with equivalent power but no run-in period.